Kinetics of Nucleation-controlled Polymerization. A Perturbation Treatment for Use with a Secondary Pathway

We present a perturbation method for analyzing nucleation-controlled polymerization augmented by a secondary pathway for polymer growth. With this method, the solution to the kinetic equations assumes a simple analytic closed form that can easily be used in fitting data. So long as the formation of polymers by the secondary pathway depends linearly on the concentration of monomers polymerized, the form of the solutions is the same. This permits the analysis of augmented growth models with a minimum number of modeling assumptions, and thus makes it readily possible to distinguish between a variety of secondary processes (heterogeneous nucleation, lateral growth, and fragmentation). In addition, the parameters of the homogeneous process, such as the homogeneous nucleus size, can be determined independent of the nature of the secondary mechanism. We describe applications of this method to the polymerization of actin, collagen, and sickle hemoglobin. We present an extensive analysis of data on actin polymerization (Wegner, A., and P. Savko, 1982, Biochemistry, 21:1909-1913) to illustrate the use of the method. Although our conclusions generally agree with theirs, we find that lateral growth describes the secondary pathway better than the fragmentation model originally proposed. We also show how this method can be used to study the degree of polymerization, the parentage of polymers, and the behavior of polymers in cycling experiments.